The investigations proposed here seek to gain understanding of the physiology of host defense against bacterial and fungal infections, and of the biochemical basis for the predisposition to bacterial infection in certain disease states. Mechanisms involved in the interaction of bacteria and polymorphonuclear and mononuclear phagocytes and complement activated through the alternative pathway will be studied in the following specific projects: (1) Studies of the mechanism(s) of fungal killing by mononuclear phagocytes and the effect of in vivo or in vitro "activation" on these mechanisms. (2) Comparisons of activity of the enzyme superoxide dismutase in resident and activated macrophages. (3) Studies of the enzymatic basis of the phagocytic respiratory burst in neutrophils and macrophages. Attempts will be made to purify an NADPH oxidase activity from these cells. (4) Studies of complement alternative pathway activity in diseases involving the reticuloendothelial system, including sickle cell disease, post-splenectomy, malnutrition, and thalassemia. (5) Studies of the pathogenesis of meningococcal infections in patients with congenital deficiency of the sixth or seventh components of complement. This will include studies of the role of these components in phagocytic bactericidal activity.